An Ignored Resource?

In 1981, I published the first of eight review articles on the immunostimulating and antimicrobial properties of lithium and antidepressant medications. In one review I proposed that to stimulate immune function an agent must have mood-elevating properties. Thus, antidepressants and lithium may be unique in possessing this property. Let me explain how this works. Prostaglandins are tiny and short-lived -- but powerful -- molecules that self-regulate the physiology of every cell, including those of the immune system. When prostaglandins are synthesized excessively, cellular function becomes dysfunction. Prostaglandins also control the physiology, immunity, replication, and toxicity of microorganisms. The virulence of a virus is determined by the ability of its human host cell to resist it and the virus's ability to induce prostaglandin E2 synthesis. HIV is exceptionally powerful in inducing prostaglandin E2 synthesis. And when induced excessively, these molecules depress immune system function. In fact, prostaglandin E2 is thought to be the most powerful immunosuppressant produced in the body and a key contributor to HIV's ability to suppress and kill CD4 immune system cells. The failure of such standard prostaglandin inhibitors as aspirin and ibuprofen in preventing HIV from stimulating prostaglandin E2 production in lab tests led many researchers to reach the conclusion that this approach was ineffective as a potential HIV treatment. However, research conducted in the mid 1970s showed that other compounds -- specifically antidepressants ' do indeed prevent the synthesis of prostaglandin E2 or block its actions. These studies showed that lithium blocked a similar compound, called prostaglandin E1, and that both lithium and other antidepressant medications inhibited enzymes involved in the production of prostaglandins that aspirin and ibuprofen do not affect. Antidepressants also have been shown to have immunostimulating, antibacterial, antiviral, antiparasite, and fungicidal properties as well as the ability to heighten the effects of antibiotics. Specifically, lithium may be useful in treating methicillin-resistant staphylococcus aureus infections (MRSA) and hospital-acquired infections. Monoamine oxidase inhibitors (MAOIs) also may be useful in reversing various viral and bacterial infections. At least 70 published studies additionally show that antidepressants have clinically relevant anticancer actions, which is not surprising given their ability to stimulate immune function. But despite this laundry list of potential health benefits, little research has been done with regard to the use of antidepressant medications as disease and infection treatments. Perhaps that is because antidepressant medications are cheap, costing just $1 to $3 per day. It would seem, unfortunately, that medications promising to save a fortune rather than create one have little appeal to researchers. So where do we go from here? Randomized clinical trials would be highly unethical, given the pressing worldwide need for immunostimulants. Such trials also would likely involve only one or two antidepressants, and could not be generalized to the others. But similarly unethical, in my opinion, is that fact that throughout the AIDS epidemic not one prominent person or institution has come forward to support the clinical application of antidepressant medications to HIV-positive adults. We should have had answers to the following questions many years ago. Can antidepressants: > Stimulate the immune system to eradicate HIV? > Prevent HIV from replicating? > Prevent or reverse opportunistic infections? > Prevent or reverse HIV-related cancers? But instead of providing us with these answers, scientists and the media -- including both the lay media and respected medical journals -- remain silent, leaving it to HIV-positive individuals themselves to learn more about this potential resource. In that light, I urge you to do your own research on the topic. A good place to start is federal PubMed website, at www.ncbi.nlm.nih.gov/pubmed. Simply search on a few key words (among them immunostimulants, antidepressants, prostaglandin E2, and even my name, Julian Lieb) to find out more. And be sure to print out abstracts or copies of the articles and studies you find so you can show them to your doctor and discuss if antidepressant medications might be right for you. Lieb was a professor of psychiatry at Yale University and the director of the Dana Psychiatric Clinic in New Haven, Conn., before becoming an immunopharmacology researcher. He has authored or coauthored 45 articles and nine books.